Systematic Identification of Scaffolds Representing Compounds Active against Individual Targets and Single or Multiple Target Families

作者：Hu Ye; Bajorath Juergen^*

来源：Journal of Chemical Information and Modeling, 2013, 53(2): 312-326.

DOI：10.1021/ci300616s

Given the enormous growth of compound activity data we currently observe, we have revisited the previously introduced concepts of privileged substructures and community-selective scaffolds and systematically searched for molecular scaffolds representing compounds active against single targets, multiple targets belonging to the same target family, or targets belonging to different families. The influence of different types of activity measurements on scaffold assignments has been determined. Furthermore, scaffold assignments have also been carried out after applying a potency threshold to exclude weakly active compounds from the comparison and address the issue of molecular selectivity. In both instances, the results were very similar indicating that single-target and single-family scaffolds display target- and family-selective tendencies, respectively. Unexpectedly large numbers of 630 unique single-target, 489 single-family, and 336 multi-family scaffolds have been identified in public domain compound data that represented relatively large numbers of compounds. Other important findings are that most of the growth in high-confidence compound activity data has been due to the evaluation of new compounds, rather than additional measurements for previously tested compounds or analog series for previously explored scaffolds. The majority of scaffolds have remained in the same category over time. Activity measurement type-dependent sets of single-target, single-family, and multi-family scaffolds are also provided as an up-to-date scaffold knowledge base.

• 出版日期2013-2